Biological information measurement device, and biological information measurement method using same

ABSTRACT

The present invention has an object of improving the measurement accuracy in a biological information measurement device, e.g., for measuring a blood glucose level. The device is configured to be able to change at least one of i) a voltage value to be applied to the second input terminal and the third input terminal (i.e., the blood component measurement counter electrode  7  and the blood component measurement working electrode  6 ) in the second biological information measurement mode D and ii) a voltage application time during which a voltage is applied to the second input terminal and the third input terminal in the second biological information measurement mode D based on the first biological information in the first biological information measurement mode A. A hematocrit value is measured in the first biological information measurement mode A, and a glucose value is measured based on the hematocrit value in the second biological information measurement mode D.

TECHNICAL FIELD

The present invention relates to a biological information measurementdevice, e.g., for measuring a blood glucose level and a biologicalinformation measurement method using the biological informationmeasurement device.

BACKGROUND ART

A conventional biological information measurement device, e.g., formeasuring a blood glucose level has the following configuration.

The conventional biological information measurement device to which abiosensor is to be attached, the biosensor including a first electrode,a second electrode, a third electrode, and a reagent portion providedbetween the second electrode and the third electrode, includes thefollowing: a first input terminal to be connected to the firstelectrode; a second input terminal to be connected to the secondelectrode; a third input terminal to be connected to the thirdelectrode; a voltage application portion that applies a voltage to thefirst input terminal, the second input terminal, and the third inputterminal; a determination portion that is connected to the first inputterminal, the second input terminal, and the third input terminal; acontrol portion that is connected to the determination portion and thevoltage application portion; and a display portion that is connected tothe control portion (see, e.g., Patent Document 1).

PRIOR ART DOCUMENTS Patent Documents

Patent Document 1: WO 2008/047843 A1

DISCLOSURE OF INVENTION Problem to be Solved by the Invention

In the above conventional example, the biosensor is attached to thebiological information measurement device, and then a drop of blood(i.e., a biological sample) is placed on the biosensor. Subsequently, ablood glucose level is measured as biological information.

In this case, the blood glucose level to be measured varies depending onhematocrit of the blood. Therefore, in the conventional example, ahematocrit value is measured after measuring the blood glucose level,and then the blood glucose level is corrected in accordance with thehematocrit value and displayed on the display portion.

However, such a measurement may reduce the measurement accuracy of theblood glucose level due to the hematocrit value.

The blood glucose level is significantly affected by the hematocritvalue even while it is being measured. After that, if the significantlyaffected blood glucose level is tried to be corrected in accordance withthe hematocrit value, the amount of correction to the final bloodglucose level is increased. This results in low measurement accuracy ofthe corrected blood glucose level.

With the foregoing in mind, it is an object of the present invention toimprove the measurement accuracy of the biological information.

Means for Solving Problem

To achieve the above object, the present invention is directed to abiological information measurement device to which a biosensor is to beattached. The biosensor includes a first electrode, a second electrode,a third electrode, and a reagent portion provided between the secondelectrode and the third electrode. The biological informationmeasurement device includes the following: a first input terminal to beconnected to the first electrode; a second input terminal to beconnected to the second electrode; a third input terminal to beconnected to the third electrode; a voltage application portion thatapplies a voltage to the first input terminal, the second inputterminal, and the third input terminal; a control portion that isconnected to the voltage application portion; and a display portion thatis connected to the control portion. The control portion is configuredto perform a first biological information measurement mode in whichfirst biological information is measured based on a current flowingthrough the first input terminal and a second biological informationmeasurement mode in which second biological information is measured byapplying a voltage to the second input terminal and the third inputterminal after the first biological information measurement mode. Thedisplay portion is configured to display the second biologicalinformation. The control portion is configured to be able to change atleast one of i) a voltage value to be applied to the second inputterminal and the third input terminal in the second biologicalinformation measurement mode and ii) a voltage application time duringwhich a voltage is applied to the second input terminal and the thirdinput terminal in the second biological information measurement modebased on the first biological information in the first biologicalinformation measurement mode.

Moreover, the present invention is directed to a biological informationmeasurement device to which a biosensor is to be attached. The biosensorincludes a first electrode, a second electrode, a third electrode, and areagent portion provided between the second electrode and the thirdelectrode. The biological information measurement device includes thefollowing: a first input terminal to be connected to the firstelectrode; a second input terminal to be connected to the secondelectrode; a third input terminal to be connected to the thirdelectrode; a voltage application portion that applies a voltage to thefirst input terminal, the second input terminal, and the third inputterminal; a control portion that is connected to the voltage applicationportion; and a display portion that is connected to the control portion.The control portion is configured to perform a first biologicalinformation measurement mode in which first biological information ismeasured based on a current flowing through the first input terminal, apre-processing application mode in which a voltage is applied to thesecond input terminal and the third input terminal after the firstbiological information measurement mode, a voltage application stop modein which the application of the voltage to the second input terminal andthe third input terminal is stopped after the pre-processing applicationmode, and a second biological information measurement mode in whichsecond biological information is measured by applying a voltage to thesecond input terminal and the third input terminal after the voltageapplication stop mode. The display portion is configured to display thesecond biological information. The control portion is configured to beable to change a voltage value to be applied to the second inputterminal and the third input terminal in the pre-processing applicationmode based on the first biological information in the first biologicalinformation measurement mode.

Further, the present invention is directed to a biological informationmeasurement device to which a biosensor is to be attached. The biosensorincludes a first electrode, a second electrode, a third electrode, and areagent portion provided between the second electrode and the thirdelectrode. The biological information measurement device includes thefollowing: a first input terminal to be connected to the firstelectrode; a second input terminal to be connected to the secondelectrode; a third input terminal to be connected to the thirdelectrode; a voltage application portion that applies a voltage to thefirst input terminal, the second input terminal, and the third inputterminal; a control portion that is connected to the voltage applicationportion; and a display portion that is connected to the control portion.The control portion is configured to perform a first biologicalinformation measurement mode in which first biological information ismeasured based on a current flowing through the first input terminal, apre-processing application mode in which a voltage is applied to thesecond input terminal and the third input terminal after the firstbiological information measurement mode, a voltage application stop modein which the application of the voltage to the second input terminal andthe third input terminal is stopped after the pre-processing applicationmode, and a second biological information measurement mode in whichsecond biological information is measured by applying a voltage to thesecond input terminal and the third input terminal after the voltageapplication stop mode. The display portion is configured to display thesecond biological information. The control portion is configured to beable to change a voltage value to be applied to the second inputterminal and the third input terminal in the pre-processing applicationmode based on the first biological information in the first biologicalinformation measurement mode. The control portion is configured to beable to change a voltage application time during which a voltage isapplied to the second input terminal and the third input terminal in thesecond biological information measurement mode based on the firstbiological information in the first biological information measurementmode.

With these configurations, the present invention can achieve theintended purpose of improving the measurement accuracy of the biologicalinformation.

Effects of the Invention

As described above, the present invention is directed to a biologicalinformation measurement device to which a biosensor is to be attached.The biosensor includes a first electrode, a second electrode, a thirdelectrode, and a reagent portion provided between the second electrodeand the third electrode. The biological information measurement deviceincludes the following: a first input terminal to be connected to thefirst electrode; a second input terminal to be connected to the secondelectrode; a third input terminal to be connected to the thirdelectrode; a voltage application portion that applies a voltage to thefirst input terminal, the second input terminal, and the third inputterminal; a control portion that is connected to the voltage applicationportion; and a display portion that is connected to the control portion.The control portion is configured to perform a first biologicalinformation measurement mode in which first biological information ismeasured based on a current flowing through the first input terminal anda second biological information measurement mode in which secondbiological information is measured by applying a voltage to the secondinput terminal and the third input terminal after the first biologicalinformation measurement mode. The display portion is configured todisplay the second biological information. The control portion isconfigured to be able to change at least one of i) a voltage value to beapplied to the second input terminal and the third input terminal in thesecond biological information measurement mode and a voltage applicationtime during which a voltage is applied to the second input terminal andthe third input terminal in the second biological informationmeasurement mode based on the first biological information in the firstbiological information measurement mode. Thus, the present invention canimprove the measurement accuracy.

According to the present invention, at least one of the voltage value tobe applied to the second input terminal and the third input terminal inthe second biological information measurement mode and the voltageapplication time during which a voltage is applied to the second inputterminal and the third input terminal in the second biologicalinformation measurement mode can be changed based on the firstbiological information in the first biological information measurementmode. The first biological information, e.g., a hematocrit value ismeasured in the first biological information measurement mode, and thesecond biological information, e.g., a blood glucose level is measuredbased on this hematocrit value in the second biological informationmeasurement mode.

As described above, the present invention is directed to a biologicalinformation measurement device to which a biosensor is to be attached.The biosensor includes a first electrode, a second electrode, a thirdelectrode, and a reagent portion provided between the second electrodeand the third electrode. The biological information measurement deviceincludes the following: a first input terminal to be connected to thefirst electrode; a second input terminal to be connected to the secondelectrode; a third input terminal to be connected to the thirdelectrode; a voltage application portion that applies a voltage to thefirst input terminal, the second input terminal, and the third inputterminal; a control portion that is connected to the voltage applicationportion; and a display portion that is connected to the control portion.The control portion is configured to perform a first biologicalinformation measurement mode in which first biological information ismeasured based on a current flowing through the first input terminal, apre-processing application mode in which a voltage is applied to thesecond input terminal and the third input terminal after the firstbiological information measurement mode, a voltage application stop modein which the application of the voltage to the second input terminal andthe third input terminal is stopped after the pre-processing applicationmode, and a second biological information measurement mode in whichsecond biological information is measured by applying a voltage to thesecond input terminal and the third input terminal after the voltageapplication stop mode. The display portion is configured to display thesecond biological information. The control portion is configured to beable to change a voltage value to be applied to the second inputterminal and the third input terminal in the pre-processing applicationmode based on the first biological information in the first biologicalinformation measurement mode. Thus, the present invention can improvethe measurement accuracy.

According to the present invention, the voltage value to be applied tothe second input terminal and the third input terminal in thepre-processing application mode can be changed based on the firstbiological information in the first biological information measurementmode. The first biological information, e.g., a hematocrit value ismeasured in the first biological information measurement mode, and thesecond biological information, e.g., a blood glucose level is measuredbased on this hematocrit value in the second biological informationmeasurement mode.

As described above, the present invention is directed to a biologicalinformation measurement device to which a biosensor is to be attached.The biosensor includes a first electrode, a second electrode, a thirdelectrode, and a reagent portion provided between the second electrodeand the third electrode. The biological information measurement deviceincludes the following: a first input terminal to be connected to thefirst electrode; a second input terminal to be connected to the secondelectrode; a third input terminal to be connected to the thirdelectrode; a voltage application portion that applies a voltage to thefirst input terminal, the second input terminal, and the third inputterminal; a control portion that is connected to the voltage applicationportion; and a display portion that is connected to the control portion.The control portion is configured to perform a first biologicalinformation measurement mode in which first biological information ismeasured based on a current flowing through the first input terminal, apre-processing application mode in which a voltage is applied to thesecond input terminal and the third input terminal after the firstbiological information measurement mode, a voltage application stop modein which the application of the voltage to the second input terminal andthe third input terminal is stopped after the pre-processing applicationmode, and a second biological information measurement mode in whichsecond biological information is measured by applying a voltage to thesecond input terminal and the third input terminal after the voltageapplication stop mode. The display portion is configured to display thesecond biological information. The control portion is configured to beable to change a voltage value to be applied to the second inputterminal and the third input terminal in the pre-processing applicationmode based on the first biological information in the first biologicalinformation measurement mode. The control portion is configured to beable to change a voltage application time during which a voltage isapplied to the second input terminal and the third input terminal in thesecond biological information measurement mode based on the firstbiological information in the first biological information measurementmode. Thus, the present invention can improve the measurement accuracy.

According to the present invention, the voltage value to be applied tothe second input terminal and the third input terminal in thepre-processing application mode can be changed based on the firstbiological information in the first biological information measurementmode, and the voltage application time during which a voltage is appliedto the second input terminal and the third input terminal in the secondbiological information measurement mode can be changed based on thefirst biological information in the first biological informationmeasurement mode. The first biological information, e.g., a hematocritvalue is measured in the first biological information measurement mode,and the second biological information, e.g., a blood glucose level ismeasured based on this hematocrit value in the second biologicalinformation measurement mode.

Therefore, according to the present invention, since the secondbiological information (e.g., the blood glucose level) itself ismeasured under the conditions that are not much affected by the firstbiological information (e.g., the hematocrit value), the measurementaccuracy can be improved.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is an electrical block diagram of a biological informationmeasurement device of an embodiment of the present invention.

FIG. 2A is an exploded perspective view of a biosensor used for abiological information measurement device of an embodiment of thepresent invention.

FIG. 2B is a cross-sectional view of a biosensor used for a biologicalinformation measurement device of an embodiment of the presentinvention.

FIG. 3 is an operational flowchart of a biological informationmeasurement device of an embodiment of the present invention.

FIG. 4 is a diagram showing the state of a voltage applied over time ina biological information measurement device of an embodiment of thepresent invention.

FIG. 5 is a graph showing a change in a response current value (μA) overtime in accordance with the application of a voltage in a biologicalinformation measurement device of an embodiment of the presentinvention.

FIG. 6 is a graph showing a change in a response current value (μA) overtime in accordance with the application of a voltage in a biologicalinformation measurement device of an embodiment of the presentinvention.

FIG. 7 is a graph showing a change in an output voltage (mV) with ablood glucose level in a biological information measurement device of anembodiment of the present invention.

FIG. 8 is a graph showing a difference in sensitivity of an outputvoltage (mV) with respect to a hematocrit value in a biologicalinformation measurement device of an embodiment of the presentinvention.

FIG. 9 is a graph showing a difference in sensitivity of an outputvoltage (mV) with respect to a hematocrit value in a biologicalinformation measurement device of an embodiment of the presentinvention.

FIG. 10 is a graph showing a difference in sensitivity of an outputvoltage (mV) with respect to a hematocrit value in a biologicalinformation measurement device of an embodiment of the presentinvention.

FIG. 11 is a graph showing a change in an output voltage (mV) with ablood glucose level in a biological information measurement device of aconventional example.

FIG. 12 is a graph showing a difference in sensitivity of an outputvoltage (mV) with respect to a hematocrit value in a biologicalinformation measurement device of a conventional example.

FIG. 13 is a graph showing a difference in sensitivity of an outputvoltage (mV) with respect to a hematocrit value in a biologicalinformation measurement device of a conventional example.

FIG. 14 is a graph showing a difference in sensitivity of an outputvoltage (mV) with respect to a hematocrit value in a biologicalinformation measurement device of a conventional example.

FIG. 15 is a diagram showing the state of a voltage applied over time ina biological information measurement device of another embodiment of thepresent invention.

FIG. 16 is a graph showing a change in a response current value (μA)over time in accordance with the application of a voltage in abiological information measurement device of another embodiment of thepresent invention.

FIG. 17 is a graph showing a change in a response current value (μA)over time in accordance with the application of a voltage in abiological information measurement device of another embodiment of thepresent invention.

FIG. 18 is a graph showing a change in an output voltage (mV) with ablood glucose level in a biological information measurement device ofanother embodiment of the present invention.

FIG. 19 is a graph showing a difference in sensitivity of an outputvoltage (mV) with respect to a hematocrit value in a biologicalinformation measurement device of another embodiment of the presentinvention.

FIG. 20 is a graph showing a difference in sensitivity of an outputvoltage (mV) with respect to a hematocrit value in a biologicalinformation measurement device of another embodiment of the presentinvention.

FIG. 21 is a graph showing a difference in sensitivity of an outputvoltage (mV) with respect to a hematocrit value in a biologicalinformation measurement device of another embodiment of the presentinvention.

FIG. 22 is an operational flowchart of a biological informationmeasurement device of another embodiment of the present invention.

FIG. 23 is a diagram showing the state of a voltage applied over time ina biological information measurement device of yet another embodiment ofthe present invention.

FIG. 24 is a diagram showing the state of a voltage applied over time ina biological information measurement device of yet another embodiment ofthe present invention.

FIG. 25 is a diagram showing the state of a voltage applied over time ina biological information measurement device of yet another embodiment ofthe present invention.

FIG. 26 is a diagram showing the state of a voltage applied over time ina biological information measurement device of yet another embodiment ofthe present invention.

FIG. 27 is a diagram showing the state of a voltage applied over time ina biological information measurement device of yet another embodiment ofthe present invention.

DESCRIPTION OF THE INVENTION

Hereinafter, an embodiment of the present invention that is applied to abiological information measurement device for measuring a blood glucoselevel will be described with reference to the accompanying drawings.

Embodiment 1

FIG. 1 is an electrical block diagram of a biological informationmeasurement device of an embodiment of the present invention. FIG. 2A isan exploded perspective view of a biosensor used for a biologicalinformation measurement device of an embodiment of the presentinvention. FIG. 2B is a cross-sectional view of a biosensor used for abiological information measurement device of an embodiment of thepresent invention. As shown in FIG. 1, an insertion port 3 for abiosensor 2 is provided at one end of a main body case 1 of thebiological information measurement device.

As shown in an example of FIG. 2A, the biosensor 2 includes arectangular insulating substrate 4 and four electrodes formed on theinsulating substrate 4. The four electrodes, i.e., a hematocritmeasurement working electrode (an example of a first electrode) 5, ablood component measurement working electrode (an example of a thirdelectrode) 6, a blood component measurement counter electrode (anexample of a second electrode) 7, and a blood component introductiondetecting electrode 8 are arranged opposite each other with apredetermined space between them. Examples of the biological informationto be measured by the biological information measurement device of thepresent invention include a glucose value, a lactic acid value, a uricacid value, a bilirubin value, and a cholesterol value. Biologicalsamples used to obtain the biological information may be, e.g., blood,urine, and sweat. The biosensor 2 is an example when the biologicalsample is blood.

In the biosensor 2, each of the hematocrit measurement working electrode5, the blood component measurement working electrode 6, the bloodcomponent measurement counter electrode 7, and the blood componentintroduction detecting electrode 8 at one end of the insulatingsubstrate 4 (i.e., at the right end of FIG. 2) comes into contact withan input terminal portion 9 shown in FIG. 1, so that the biosensor 2 iselectrically connected to the biological information measurement device.

The biosensor 2 further includes a reagent portion 10 provided on anelectrode portion that is formed of the blood component measurementworking electrode 6, the blood component measurement counter electrode7, and the blood component introduction detecting electrode 8.

In the biosensor 2, a reagent 11 is placed in the reagent portion 10.The reagent 11 contains an oxidoreductase such as glucose dehydrogenaseand a mediator (electron carrier), and selectively contains a polymericmaterial, an enzyme stabilizer, and a crystal homogenizing agent asoptional components. In the biosensor 2, a cover 13 is disposed on theinsulating substrate 4 and the reagent 11 via a spacer 12, while leavingone end of the insulating substrate 4 uncovered.

The spacer 12 of the biosensor 2 has a blood supply path 14 forintroducing blood. The blood supply path 14 extends from the other endof the biosensor 2 (i.e., the left end of FIG. 2) to the position abovethe reagent 11. The other end of the blood supply path 14 is open to theoutside and serves as a blood inlet 15.

The hematocrit measurement working electrode 5, the blood componentmeasurement working electrode 6, the blood component measurement counterelectrode 7, and the blood component introduction detecting electrode 8extend to one end of the biosensor 2 (i.e., the right end of FIG. 2),where the portions of the hematocrit measurement working electrode 5,the blood component measurement working electrode 6, the blood componentmeasurement counter electrode 7, and the blood component introductiondetecting electrode 8 are not covered with the cover 13 and exposed.

Moreover, one end of each of these electrodes is connected to the inputterminal portion 9 shown in FIG. 1.

Specifically, in the biosensor 2, the hematocrit measurement workingelectrode 5 is connected to a first input terminal (not shown) of theinput terminal portion 9, the blood component measurement workingelectrode 6 is connected to a third input terminal (not shown) of theinput terminal portion 9, the blood component measurement counterelectrode 7 is connected to a second input terminal (not shown) of theinput terminal portion 9, and the blood component introduction detectingelectrode 8 is connected to a fourth input terminal (not shown) of theinput terminal portion 9.

As can also be seen from FIG. 2, in the biosensor 2, the hematocritmeasurement working electrode 5 is located closest to the blood inlet15, followed by the blood component measurement counter electrode 7, theblood component measurement working electrode 6, and the blood componentintroduction detecting electrode 8.

That is, in the biosensor 2, the hematocrit measurement workingelectrode (an example of the first electrode) 5, the blood componentmeasurement counter electrode (an example of the second electrode) 7,the blood component measurement working electrode (an example of thethird electrode) 6, and the blood component introduction detectingelectrode 8 are arranged in this order from the blood inlet 15 side.

The cover 13 of the biosensor 2 has an air hole 16 in order to promote acapillary action when a drop of blood is placed on the blood inlet 15and to allow the blood to come into the blood component introductiondetecting electrode 8.

Next, the configuration of the biosensor 2 will be described in moredetail.

In the present invention, the material of the insulating substrate 4 isnot particularly limited and may be, e.g., polyethylene terephthalate(PET), polycarbonate (PC), polyimide (PI), polyethylene (PE),polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC),polyoxymethylene (POM), monomer-cast nylon (MC), polybutyleneterephthalate (PBT), methacrylate resin (PMMA), ABS resin (ABS), orglass. Among them, polyethylene terephthalate (PET), polycarbonate (PC),polyimide (PI) are preferred, and polyethylene terephthalate (PET) ismore preferred.

The size of the insulating substrate 4 is not particularly limited. Forexample, the insulating substrate 4 has a total length of 5 to 100 mm, awidth of 2 to 50 mm, and a thickness of 0.05 to 2 mm, preferably has atotal length of 7 to 50 mm, a width of 3 to 20 mm, and a thickness of0.1 to 1 mm, and more preferably has a total length of 10 to 30 mm, awidth of 3 to 10 mm, and a thickness of 0.1 to 0.6 mm.

The electrodes on the insulating substrate 4 can be produced, e.g.,using a material such as gold, platinum, or palladium, forming aconductive layer by sputtering or evaporation, and processing theconductive layer into a particular electrode pattern with a laser. Thelaser may be, e.g., a YAG laser, a CO₂ laser, or an excimer laser. Theelectrode pattern is not limited to that disclosed in the presentinvention, and any electrode pattern is available as long as it canachieve the effects of the present invention. The electrodes of thebiosensor 2 used in the present invention may be coated with a polymericmaterial in order to prevent adhesion of impurities, oxidation, or thelike. The coating on the surface of the electrodes can be performed,e.g., by preparing a solution of the polymeric material, dropping orapplying the solution to the surface of the electrodes, and drying thesolution. The drying process may be, e.g., natural drying, air drying,hot air drying, or drying by heating.

The electron carrier of the biosensor 2 is not particularly limited andmay be, e.g., ferricyanide, p-benzoquinone, p-benzoquinone derivative,phenazine methosulfate, methylene blue, ferrocene, or ferrocenederivative. Among them, ferricyanide is preferred, and potassiumferricyanide is more preferred. The amount of the electron carrier to bemixed is not particularly limited and may be, e.g., 0.1 to 1000 mM,preferably 1 to 500 mM, and more preferably 10 to 200 mM per onemeasurement or one biosensor.

In the present invention, the first biological information is, e.g., ahematocrit value, and the second biological information is, e.g., aglucose value, a lactic acid value, a uric acid value, a bilirubinvalue, or a cholesterol value. The oxidoreductase of the presentinvention may be appropriately selected according to the type of thesecond biological information. Examples of the oxidoreductase includeglucose oxidase, lactate oxidase, cholesterol oxidase, bilirubinoxidase, glucose dehydrogenase, and lactate dehydrogenase. The amount ofthe oxidoreductase is, e.g., 0.01 to 100 U, preferably 0.05 to 10 U, andmore preferably 0.1 to 5 U per one sensor or one measurement. Inparticular, the glucose value is preferred as the second biologicalinformation, and the glucose oxidase and the glucose dehydrogenase arepreferred as the oxidoreductase.

The reagent 11 of the present invention can be produced in the followingmanner. For example, 0.1 to 5.0 U per sensor of flavin adenosinedinucleotide-dependent glucose dehydrogenase (FAD-GDH), 10 to 200 mM ofpotassium ferricyanide, 1 to 50 mM of maltitol, and 20 to 200 mM oftaurine are added to and dissolved in a 0.01 to 2.0 wt % carboxymethylcellulose (CMC) aqueous solution to prepare a reagent solution. Then,the reagent solution is dropped onto the electrodes of the insulatingsubstrate 4 and dried.

Next, in the present invention, the material of the spacer 12 is notparticularly limited and may be, e.g., the same as that of theinsulating substrate 4. The size of the spacer 12 is not particularlylimited. For example, the spacer 12 has a total length of 5 to 100 mm, awidth of 2 to 50 mm, and a thickness of 0.01 to 1 mm, preferably has atotal length of 7 to 50 mm, a width of 3 to 20 mm, and a thickness of0.05 to 0.5 mm, and more preferably has a total length of 10 to 30 mm, awidth of 3 to 10 mm, and a thickness of 0.05 to 0.25 mm. The spacer 12has an I-shaped notch that serves as the blood supply path 14 forintroducing blood. The blood supply path 14 may be, e.g., in the form ofa T-shaped notch. In such a case, the present invention can also becarried out by appropriately providing a reagent portion and anelectrode portion at each end of the blood supply path to perform ahematocrit measurement and a glucose measurement separately.

In the present invention, the material of the cover 13 is notparticularly limited and may be, e.g., the same as that of theinsulating substrate 4. It is more preferable that a portion of thecover 13 that forms the ceiling of the blood supply path 14 is subjectedto a hydrophilic treatment. The hydrophilic treatment may be, e.g., amethod for applying a surface active agent or a method for introducing ahydrophilic functional group such as a hydroxyl group, a carbonyl group,or a carboxyl group into the surface of the cover 13 by plasmaprocessing. The size of the cover 13 is not particularly limited. Forexample, the cover 13 has a total length of 5 to 100 mm, a width of 3 to50 mm, and a thickness of 0.01 to 0.5 mm, preferably has a total lengthof 10 to 50 mm, a width of 3 to 20 mm, and a thickness of 0.05 to 0.25mm, and more preferably has a total length of 15 to 30 mm, a width of 5to 10 mm, and a thickness of 0.05 to 0.1 mm. The cover 13 preferably hasthe air hole 16, e.g., in the form of a circle, ellipse, or polygon. Theair hole 16 may have, e.g., a maximum diameter of 0.01 to 10 mm,preferably a maximum diameter of 0.05 to 5 mm, and more preferably amaximum diameter of 0.1 to 2 mm. The air hole 16 may be formed, e.g., bypunching through the cover 13 with a laser or drill, or by using a diethat enables an air vent to be provided during the formation of thecover 13.

Next, as shown in FIG. 2, the insulating substrate 4, the spacer 12, andthe cover 13 are laminated in this order and integrated into onecomponent, thereby producing the biosensor 2. For the integration, thethree members may be joined using an adhesive or thermally fusedtogether. Examples of the adhesive include an epoxy adhesive, an acrylicadhesive, a polyurethane adhesive, a thermosetting adhesive (such as ahot-melt adhesive), and a UV curable adhesive.

Referring back to FIG. 1 again, a voltage application portion 17 forapplying a voltage and a current-voltage converter 18 are connected tothe input terminal portion 9 of the biological information measurementdevice of an embodiment of the present invention.

A voltage is supplied from a control portion 19 to the voltageapplication portion 17, and this voltage is then applied via the inputterminal portion 9 to a desired electrode among the hematocritmeasurement working electrode 5, the blood component measurement workingelectrode 6, the blood component measurement counter electrode 7, andthe blood component introduction detecting electrode 8 of the biosensor2 for a predetermined time. The current flowing between the electrodesof the biosensor 2 as a result of this voltage application is convertedto a voltage by the current-voltage converter 18, and subsequently thevoltage is converted to a digital value by an analog-digital (A/D)converter 20. Thereafter, a determination portion 21 compares thedigitized voltage value with a threshold value.

A display portion 22 is connected to the control portion 19 and displaysthe glucose value detected by the biosensor 2 and the results of thedetermination made by the determination portion 21.

In FIG. 1, reference numeral 23 denotes a power source that suppliespower to each portion. Reference numeral 24 denotes a memory that storesa table containing hematocrit values (the first biological information)and applied voltages, application times, etc. for measuring the glucose,or a calibration curve and a calibration table that have been previouslyprepared from the ambient temperature.

A clock 25 is connected to the control portion 19. The control portion19 makes use of the hour and the time of the clock 25 to perform variouscontrol operations.

The control portion 19 further includes a correction portion 26 thatcorrects the measured blood glucose level with the hematocrit value toimprove the measurement accuracy of the blood glucose level.

One of the characteristics of this embodiment is that the controlportion 19 performs a first biological information measurement mode A, apre-processing application mode B, a voltage application stop mode C,and a second biological information measurement mode D, as shown in FIG.4. FIG. 4 is a diagram showing the state of a voltage applied over timein a biological information measurement device of an embodiment of thepresent invention.

In the first biological information measurement mode A of thisembodiment, the first biological information (the hematocrit value) ismeasured based on the current flowing through the first input terminal(not shown) of the input terminal portion 9, i.e., the hematocritmeasurement working electrode 5.

In the pre-processing application mode B of this embodiment, a voltageis applied to the second input terminal (not shown) and the third inputterminal (not shown) of the input terminal portion 9 in FIG. 1, i.e.,the blood component measurement counter electrode 7 and the bloodcomponent measurement working electrode 6 after the first biologicalinformation measurement mode A.

In the voltage application stop mode C of this embodiment, theapplication of the voltage to the second input terminal (not shown) andthe third input terminal (not shown) of the input terminal portion 9,i.e., the blood component measurement counter electrode 7 and the bloodcomponent measurement working electrode 6 is stopped after thepre-processing application mode B.

In the second biological information measurement mode D of thisembodiment, the second biological information (the glucose value) ismeasured by applying a voltage to the second input terminal (not shown)and the third input terminal (not shown) of the input terminal portion9, i.e., the blood component measurement counter electrode 7 and theblood component measurement working electrode 6 after the voltageapplication stop mode C.

In this embodiment, the control portion 19 is configured to be able tochange the voltage to be applied to the second input terminal (notshown) and the third input terminal (not shown) of the input terminalportion 9, i.e., the blood component measurement counter electrode 7 andthe blood component measurement working electrode 6 in thepre-processing application mode B based on the first biologicalinformation (the hematocrit value) in the first biological informationmeasurement mode A.

FIG. 5 is a graph showing a change in a response current value (μA) overtime in accordance with the application of a voltage in a biologicalinformation measurement device of this embodiment. Specifically, FIG. 5illustrates the properties of the first biological informationmeasurement mode A, the pre-processing application mode B, the voltageapplication stop mode C, and the second biological informationmeasurement mode D when the hematocrit values (the first biologicalinformation) are 20%, 45%, and 60% in the above configuration. FIG. 5shows the response current value (μA) in each mode. As shown in FIG. 5,the response current value is low when the hematocrit value is high(e.g., 60%), and the response current value is high when the hematocritvalue is low (e.g., 20%).

This is because if blood has a high hematocrit value (high Hct value),the viscosity of the blood is increased and the current response isrelatively reduced; if blood has a low hematocrit value (low Hct value),the viscosity of the blood is reduced and the current response isrelatively increased.

In FIG. 5, it may be difficult to understand the response currentchanges in the pre-processing application mode B and the secondbiological information measurement mode D. FIG. 6 is an enlarged view ofthe response current changes in these modes. As can be sheen from FIG.6, the pre-processing application mode B and the second biologicalinformation measurement mode D also have the properties similar to thoseof the first biological information measurement mode A That is, if bloodhas a high hematocrit value (high Hct value), the viscosity of the bloodis increased and the current response is relatively reduced; if bloodhas a low hematocrit value (low Hct value), the viscosity of the bloodis reduced and the current response is relatively increased.

Next, referring to FIGS. 2 and 3, the measurement flow in the firstbiological information measurement mode A, the pre-processingapplication mode B, the voltage application stop mode C, and the secondbiological information measurement mode D will be described in moredetail. FIG. 3 is an operational flowchart of a biological informationmeasurement device of this embodiment.

Before use, a plurality of biosensors 2 (shown in FIG. 2) are stored ina dry container (not shown). The biosensors 2 are taken out of the drycontainer one by one every time the glucose value (i.e., the bloodglucose level or the second biological information) is measured. Then,as shown in FIG. 1, one end of the biosensor 2 is inserted into theinsertion port 3 (S1: “Attach biosensor” in FIG. 3) and electricallyconnected to the input terminal portion 9. Consequently, the controlportion 19 recognizes that the biosensor 2 has been attached to theinput terminal portion 9, and starts a measuring operation (S2:“Activate power source of measurement device” in FIG. 3).

In this state, a drop of blood of a user has not been placed on theblood inlet 15 yet.

With the start of the measuring operation, the control portion 19 allowsan applied voltage to be supplied to each of the blood componentmeasurement working electrode 6, the blood component measurement counterelectrode 7, and the blood component introduction detecting electrode 8of the biosensor 2 via the voltage application portion 17 and the inputterminal portion 9 (S3: “Apply voltage to measurement working electrode,measurement counter electrode, and detecting electrode” in FIG. 3).

In this embodiment, the applied voltage supplied to each of the bloodcomponent measurement working electrode 6, the blood componentmeasurement counter electrode 7, and the blood component introductiondetecting electrode 8 is, e.g., 0.5 V.

Next, a user pricks their finger or the like with a lancet to draw bloodand places a drop of blood on the blood inlet 15 of the biosensor 2 (S4:“Place drop of blood on inlet of biosensor” in FIG. 3).

Then, a current begins to flow between the blood component measurementworking electrode 6 and the blood component measurement counterelectrode 7 and between the blood component measurement workingelectrode 6 and the blood component introduction detecting electrode 8.This current is converted to a voltage by the current-voltage converter18, and subsequently the voltage is converted to a digital value by theA/D converter 20. Thereafter, the determination portion 21 of thecontrol portion 19 makes a determination.

Specifically, the control portion 19 measures a value of the currentflowing between the blood component measurement working electrode 6 andthe blood component measurement counter electrode 7, and compares avoltage value that is proportional to the current value with apredetermined threshold value (e.g., 10 mV). If the voltage value is notless than the threshold value, then the control portion 19 measures avalue of the current flowing between the blood component measurementworking electrode 6 and the blood component introduction detectingelectrode 8.

If the voltage value that is proportional to the value of the currentflowing between the blood component measurement working electrode 6 andthe blood component measurement counter electrode 7 is less than thethreshold value, the determination portion 21 of the control portion 19determines that the drop of blood still has not sufficiently permeatedthe reagent 11, and repeats the above comparison until the value of thecurrent flowing between the blood component measurement workingelectrode 6 and the blood component measurement counter electrode 7 isnot less than the threshold value (S5: “Current flowing betweenmeasurement working electrode and measurement counter electrode≥Threshold value” in FIG. 3).

Similarly, the control portion 19 measures a value of the currentflowing between the blood component measurement working electrode 6 andthe blood component introduction detecting electrode 8, compares avoltage value that is proportional to the current value with apredetermined threshold value (e.g., 10 mV), and determines whether thevoltage value is not less than the threshold value. If the current valueis less than the threshold value, it is determined that the drop ofblood still has not sufficiently permeated the reagent 11 and the bloodcomponent introduction detecting electrode 8, and the above comparisonis repeated until the current value is not less than the threshold value(S6: “Current flowing between measurement working electrode anddetecting electrode ≥Threshold value” in FIG. 3).

Then, if the current value is not less than the threshold value in thestep S5 and the following step S6 in FIG. 3, the determination portion21 of the control portion 19 determines that the amount of the bloodthat has been introduced is large enough to be measured.

Next, when it is determined that the amount of the blood that has beenintroduced is large enough to be measured, the control portion 19applies, e.g., a voltage of 1.0 to 3.0 V (the applied voltage is 2.5 Vinthis embodiment) between the hematocrit measurement working electrode 5and the blood component measurement counter electrode 7 for anapplication time of 0.01 to 3.0 seconds (the application time is 0.5seconds in this embodiment) in the first biological informationmeasurement mode A (S7: “Apply voltage between hematocrit workingelectrode and measurement counter electrode to calculate hematocritvalue” in FIG. 3).

As can be seen from FIG. 2, there is a certain space (e.g., 0.01 mm to10 mm) between the hematocrit measurement working electrode 5 and theblood component measurement counter electrode 7, and no reagent such asan electron carrier is present in this space.

Therefore, an oxidation current that depends on the hematocrit value(the first biological information) can be detected without the influenceof the reagent 11 between the hematocrit measurement working electrode 5and the blood component measurement counter electrode 7.

The oxidation current is recognized as a voltage value by the controlportion 19 via the current-voltage converter 18 and the A/D converter20.

One of the characteristics of this embodiment is that the voltage to beapplied in the pre-processing application mode B can be changed based onthe oxidation current (which has been converted to a voltage value) thatdepends on the hematocrit value (the first biological information) andis recognized by the control portion 19.

Specifically, in this embodiment, the voltage to be applied in thepre-processing application mode B can be determined according to theoxidation current (which has been converted to a voltage value) thatdepends on the detected hematocrit value (the first biologicalinformation), using a management table containing hematocrit values (thefirst biological information) and applied voltages, application times,etc. for measuring the glucose, which has been previously stored in thememory 24.

In other words, if blood has a high hematocrit value (high Hct value),the viscosity of the blood is increased and the current response isrelatively reduced during the measurement of the glucose. Therefore, thehigh-Hct blood requires a voltage to achieve a high current response. Ifblood has a low hematocrit value (low Hct value), the viscosity of theblood is reduced and the current response is relatively increased duringthe measurement of the glucose. Therefore, the low-Hct blood requires avoltage to achieve a low current response.

In this embodiment, e.g., the memory 24 stores settings of 0.75 V for ahematocrit value (the first biological information) of 20%, 0.35 V for ahematocrit value of 45%, and 0.15 V for a hematocrit value of 60%. Thecontrol portion 19 appropriately selects the voltage to be appliedaccording to these hematocrit values (S8: “Determine pre-processingvoltage to be applied according to hematocrit value” in FIG. 3). In thisembodiment, the voltage to be applied according to the above hematocritvalues may be modified by the ambient temperature. The ambienttemperature can be measured by a conventionally known method formeasuring the ambient temperature, which will be described later. Such amodification is made because the reaction between the glucose in theblood and the oxidoreductase is an enzyme reaction that is affected bythe ambient temperature. Similarly, the predetermined time during whicha voltage is applied may also be modified by the ambient temperature.

In this embodiment, when the hematocrit value (the first biologicalinformation) represents a first hematocrit value in the memory 24, afirst voltage is applied to the second input terminal and the thirdinput terminal in the pre-processing application mode, and when thehematocrit value represents a second hematocrit value in the memory 24,a second voltage is applied to the second input terminal and the thirdinput terminal in the pre-processing application mode. The firsthematocrit value may be selected to be larger than the second hematocritvalue, and the first voltage may be selected to be smaller than thesecond voltage.

Alternatively, in this embodiment, when the hematocrit value (the firstbiological information) represents a first hematocrit value in thememory 24, a first voltage is applied to the second input terminal andthe third input terminal in the pre-processing application mode, whenthe hematocrit value represents a second hematocrit value in the memory24, a second voltage is applied to the second input terminal and thethird input terminal in the pre-processing application mode, and whenthe hematocrit value represents a third hematocrit value in the memory24, a third voltage is applied to the second input terminal and thethird input terminal in the pre-processing application mode. The firsthematocrit value may be selected to be larger than the second hematocritvalue and the third hematocrit value, and the second hematocrit valuemay be selected to be larger than the third hematocrit value. The firstvoltage may be selected to be smaller than the second voltage and thethird voltage, and the second voltage may be selected to be smaller thanthe third voltage.

Next, in this embodiment, the control portion 19 applies the voltagethat has been determined according to the measured hematocrit value (thefirst biological information) between the blood component measurementworking electrode 6 and the blood component measurement counterelectrode 7, e.g., for a predetermined time of 0.5 to 4.0 seconds (for2.0 seconds in this embodiment) in the pre-processing application mode B(S9: “Apply determined voltage between measurement working electrode andmeasurement counter electrode” in FIG. 3).

Thereafter, in this embodiment, the control portion 19 stops theapplication of the voltage to all the electrodes (the hematocritmeasurement working electrode 5, the blood component measurement workingelectrode 6, the blood component measurement counter electrode 7, andthe blood component introduction detecting electrode 8) of the biosensor2 for about 0.1 to 5.0 seconds (for 1.0 second in this embodiment) inorder to further accelerate the reaction between the glucose in theblood and the reagent 11 containing the oxidoreductase and the electroncarrier in the voltage application stop mode C (S10: “Stop voltageapplication” in FIG. 3).

Then, in the voltage application stop mode C, the glucose in the bloodreacts with the oxidoreductase for a certain period of time.

In the next second biological information measurement mode D, thecontrol portion 19 applies a voltage between the blood componentmeasurement working electrode 6 and the blood component measurementcounter electrode 7, oxidizes the reduced electron carrier that isgenerated on the blood component measurement working electrode 6 by theenzyme reaction, and detects the oxidation current, thereby measuring aglucose (blood glucose) value (the second biological information).

The reaction time between the glucose and the oxidoreductase in thesecond biological information measurement mode D is, e.g., 0.5 to 20seconds, and more preferably 0.5 to 10 seconds. In this embodiment, avoltage of 0.05 to 1.0 V, and more preferably a voltage of 0.1 to 0.8 V(0.25 V in this embodiment) is applied between the blood componentmeasurement working electrode 6 and the blood component measurementcounter electrode 7 for 1.5 seconds.

In this embodiment, the control portion 19 calculates the glucose value(the second biological information) after an application time of 1.5seconds has elapsed (S11: “Apply voltage finally between measurementworking electrode and measurement counter electrode” in FIG. 3).

In this embodiment, the calculated glucose value (the second biologicalinformation) is subjected to a conventionally known temperaturecorrection (S12: “Measure and correct glucose value” in FIG. 3).

The temperature correction is performed because the enzyme reaction formeasuring the glucose value is affected by the ambient temperature.However, in the step S8 of determining a pre-processing voltage to beapplied according to the hematocrit value, as shown in FIG. 3, if thevoltage to be applied and/or the application time according to thehematocrit value are modified by the ambient temperature, the glucosevalue may be either corrected or not corrected at this stage. On theother hand, in the step S8 of determining a pre-processing voltage to beapplied according to the hematocrit value, as shown in FIG. 3, if thevoltage to be applied and the application time according to thehematocrit value are not modified by the ambient temperature, theglucose value needs to be corrected at this stage.

The glucose value thus corrected is displayed on the display portion 22as a final glucose (blood glucose) value (the second biologicalinformation) (S13: “Display glucose value” in FIG. 3).

One of the characteristics of this embodiment is that the voltage to beapplied in the pre-processing application mode B can be changed based onthe oxidation current (which has been converted to a voltage value) thatdepends on the hematocrit value (the first biological information) andis recognized by the control portion 19. Consequently, the blood glucoselevel displayed on the display portion 22 can achieve extremely highaccuracy.

Hereinafter, this point will be described with reference to FIGS. 7 to14.

FIG. 7 is a graph showing a change in an output voltage (mV) with ablood glucose level in a biological information measurement device of anembodiment of the present invention. Specifically, in this embodiment,FIG. 7 illustrates how the output of the A/D converter 20 (FIG. 1) ischanged with the blood glucose level in the second biologicalinformation measurement mode D when the hematocrit values are 20%, 45%,and 60% (corresponding to the state before the correction in the stepS12 in FIG. 3). As can be seen from FIG. 7, the output voltage increaseswith increasing the blood glucose level no matter whether the hematocritvalue is 20%, 45%, or 60%.

On the other hand, FIG. 11 is a graph showing a change in an outputvoltage (mV) with a blood glucose level in a biological informationmeasurement device of a conventional example. Specifically, in theconventional example, FIG. 11 illustrates how the output of the A/Dconverter 20 (FIG. 1) is changed with the blood glucose level in thesecond biological information measurement mode D when the hematocritvalues are 20%, 45%, and 60%. As can be seen from FIG. 11, similarly toFIG. 7, the output voltage increases with increasing the blood glucoselevel no matter whether the hematocrit value is 20%, 45%, or 60%.

Comparing FIG. 7 (this embodiment) and FIG. 11 (the conventionalexample) shows that a variation in the detected blood glucose level (thesecond biological information) is small even if the hematocrit values(the first biological information) differ in this embodiment. Forexample, in FIG. 11 (the conventional example), when the blood glucoselevel is 350 mg/dl, the output voltage is 280 mV for a hematocrit valueof 45%, but the output voltage is increased to 390 mV for a hematocritvalue of 20%, resulting in a difference of 110 mV.

Moreover, in FIG. 11 (the conventional example), while the outputvoltage is 280 mV for a hematocrit value of 45%, the output voltage isreduced to 200 mV for a hematocrit value of 60%, resulting in adifference of 80 mV.

On the other hand, in FIG. 7 (this embodiment), when the blood glucoselevel is 350 mg/dl, the output voltage is 290 mV for a hematocrit valueof 45%, and the output voltage is 360 mV for a hematocrit value of 20%,making only a difference of 70 mV.

Moreover, in FIG. 7 (this embodiment), while the output voltage is 290mV for a hematocrit value of 45%, the output voltage is 250 mV for ahematocrit value of 60%, making only a difference of 40 mV.

As a result of changing the voltage to be applied between the bloodcomponent measurement working electrode 6 and the blood componentmeasurement counter electrode 7 in the pre-processing application modeB, as shown in FIG. 4, this embodiment can reduce a difference in theoutput voltage between the hematocrit values.

In other words, this embodiment deals with the following points. Asdescribed above, if blood has a high hematocrit value (high Hct value),the viscosity of the blood is increased and the current response isrelatively reduced during the measurement of the glucose. Therefore, thehigh-Hct blood requires a voltage to achieve a high current response. Ifblood has a low hematocrit value (low Hct value), the viscosity of theblood is reduced and the current response is relatively increased duringthe measurement of the glucose. Therefore, the low-Hct blood requires avoltage to achieve a low current response.

In contrast, the conventional example applies the same voltage betweenthe blood component measurement working electrode 6 and the bloodcomponent measurement counter electrode 7 in the pre-processingapplication mode B regardless of the hematocrit value (FIG. 11), so thatthe output voltage varies greatly. FIG. 11 is a graph showing a changein an output voltage (mV) with a blood glucose level in a biologicalinformation measurement device of the conventional example.

FIG. 12 is a graph showing a difference in sensitivity of an outputvoltage (mV) with respect to a hematocrit value in a biologicalinformation measurement device of the conventional example.Specifically, FIG. 12 illustrates a difference (the degree of influence)in each of the samples with blood glucose levels of 100 mg/dl and 350mg/dl when their hematocrit values are 20% and 60% as compared to 45% inthe conventional example.

FIG. 12 (the conventional example) shows that both the samples withblood glucose levels of 100 mg/dl and 350 mg/dl have a difference of 35%or more on the hematocrit 20% side and a difference of 20% or more onthe hematocrit 60% side from the hematocrit value 45%.

Thus, in the conventional example, the output voltage of the A/Dconverter 20 varies greatly depending on the hematocrit value, as can beseen from FIGS. 11 and 12.

The conventional example also has made an attempt to calculate the finalblood glucose level by correcting the output voltage of the A/Dconverter 20 in accordance with the subsequently detected hematocritvalue.

However, in this conventional example, as shown in FIG. 13, the samplewith a blood glucose level of 100 mg/dl has a variation of +7.5% to−4.0% when the hematocrit value is 20%, a variation of +9.0% to −5.0%when the hematocrit value is 45%, and a variation of +9.5% to −7.0% whenthe hematocrit value is 60%. FIG. 13 is a graph showing a difference insensitivity of an output voltage (mV) with respect to a hematocrit valuein a biological information measurement device of the conventionalexample.

As shown in FIG. 14, the sample with a blood glucose level of 350 mg/dlhas a variation of +8.0% to −4.0% when the hematocrit value is 20%, avariation of +10.0% to −6.0% when the hematocrit value is 45%, and avariation of +11.0% to −7.5% when the hematocrit value is 60%. FIG. 14is a graph showing a difference in sensitivity of an output voltage (mV)with respect to a hematocrit value in a biological informationmeasurement device of the conventional example.

Even if subsequent corrections are performed while there is such a greatvariation, the final blood glucose level will still vary significantly.

Thus, the measurement accuracy is low in the conventional biologicalinformation measurement device.

Contrary to the conventional example, FIG. 8 is a graph showing adifference in sensitivity of an output voltage (mV) with respect to ahematocrit value in a biological information measurement device of thisembodiment. Specifically, FIG. 8 illustrates a difference (the degree ofinfluence) in each of the samples with blood glucose levels of 100 mg/dland 350 mg/dl when their hematocrit values are 20% and 60% as comparedto 45% in this embodiment.

FIG. 8 (this embodiment) shows that both the samples with blood glucoselevels of 100 mg/dl and 350 mg/dl have only a difference of about 20% onthe hematocrit 20% side and only a difference of about 10% on thehematocrit 60% side from the hematocrit value 45%.

Thus, in this embodiment, the output voltage of the A/D converter 20varies slightly depending on the hematocrit value, as can be seen fromFIGS. 7 and 8.

Therefore, this embodiment shows only a small variation when the finalblood glucose level is calculated from the output voltage of the A/Dconverter 20.

This point will be further described with reference to FIGS. 9 and 10.FIGS. 9 and 10 are graphs showing a difference in sensitivity of anoutput voltage (mV) with respect to a hematocrit value in a biologicalinformation measurement device of this embodiment. As shown in FIG. 9,the sample with a blood glucose level of 100 mg/dl has only a variationof +3.0% to −3.0% when the hematocrit value is 20%, only a variation of+2.0% to −3.0% when the hematocrit value is 45%, and only a variation of+5.0% to −2.0% when the hematocrit value is 60%.

As shown in FIG. 10, the sample with a blood glucose level of 350 mg/dlhas only a variation of +4.5% to −3.0% when the hematocrit value is 20%,only a variation of +4.0% to −4.0% when the hematocrit value is 45%, andonly a variation of +6.0% to −4.0% when the hematocrit value is 60%.

Therefore, in this embodiment, since the blood glucose level itself ismeasured under the conditions that are not much affected by thehematocrit value, the measurement accuracy can be improved.

This embodiment performs a temperature correction in the step S12 inFIG. 3 in order to reduce the influence of the temperature, so that themeasurement accuracy can be improved further.

In this embodiment, if the resultant hematocrit value (the firstbiological information) is a standard value (e.g., the hematocrit valueis 42), it is not necessary to change the voltage to be applied in thepre-processing application mode B and the voltage application timeduring which a voltage is applied between the blood componentmeasurement counter electrode 7 and the blood component measurementworking electrode 6 in the second biological information measurementmode D.

Embodiment 2

FIGS. 15 to 22 show Embodiment 2 of the present invention. Similarly toEmbodiment 1, Embodiment 2 can change a voltage to be applied betweenthe blood component measurement counter electrode 7 and the bloodcomponent measurement working electrode 6 in the pre-processingapplication mode B based on the hematocrit value (the first biologicalinformation) measured in the first biological information measurementmode A Moreover, Embodiment 2 can change a voltage application timeduring which a voltage is applied between the blood componentmeasurement counter electrode 7 and the blood component measurementworking electrode 6 in the second biological information measurementmode D based on the first biological information (the hematocrit value)in the first biological information measurement mode A.

FIG. 15 is a diagram showing the state of a voltage applied over time ina biological information measurement device of this embodiment. In thefirst biological information measurement mode A of FIG. 15, the firstbiological information (the hematocrit value) is measured based on thecurrent flowing through the first input terminal (not shown) of theinput terminal portion 9, i.e., the hematocrit measurement workingelectrode 5.

In the pre-processing application mode B of this embodiment, a voltageis applied to the second input terminal (not shown) and the third inputterminal (not shown) of the input terminal portion 9 in FIG. 1, i.e.,the blood component measurement counter electrode 7 and the bloodcomponent measurement working electrode 6 after the first biologicalinformation measurement mode A.

In the voltage application stop mode C of this embodiment, theapplication of the voltage to the second input terminal (not shown) andthe third input terminal (not shown) of the input terminal portion 9,i.e., the blood component measurement counter electrode 7 and the bloodcomponent measurement working electrode 6 is stopped after thepre-processing application mode B.

In the second biological information measurement mode D of thisembodiment, the second biological information (the glucose value) ismeasured by applying a voltage to the second input terminal (not shown)and the third input terminal (not shown) of the input terminal portion9, i.e., the blood component measurement counter electrode 7 and theblood component measurement working electrode 6 after the voltageapplication stop mode C.

In this embodiment, the control portion 19 is configured to be able tochange the voltage to be applied to the second input terminal (notshown) and the third input terminal (not shown) of the input terminalportion 9, i.e., the blood component measurement counter electrode 7 andthe blood component measurement working electrode 6 in thepre-processing application mode B based on the first biologicalinformation (the hematocrit value) in the first biological informationmeasurement mode A.

FIG. 16 is a graph showing a change in a response current value (μA)over time in accordance with the application of a voltage in abiological information measurement device of another embodiment of thepresent invention. Specifically, FIG. 16 illustrates the properties ofthe first biological information measurement mode A, the pre-processingapplication mode B, the voltage application stop mode C, and the secondbiological information measurement mode D when the hematocrit values are20%, 45%, and 60% in the above configuration. FIG. 16 shows the responsecurrent value (μA) in each mode. As shown in FIG. 16, the responsecurrent value is low when the hematocrit value is high (e.g., 60%), andthe response current value is high when the hematocrit value is low(e.g., 20%).

This is because if blood has a high hematocrit value (high Hct value),the viscosity of the blood is increased and the current response isrelatively reduced; if blood has a low hematocrit value (low Hct value),the viscosity of the blood is reduced and the current response isrelatively increased.

In FIG. 16, it may be difficult to understand the response currentchanges in the pre-processing application mode B and the secondbiological information measurement mode D. FIG. 17 is an enlarged viewof the response current changes in these modes. As can be seen from FIG.17, the pre-processing application mode B and the second biologicalinformation measurement mode D also have the properties similar to thoseof the first biological information measurement mode A That is, if bloodhas a high hematocrit value (high Hct value), the viscosity of the bloodis increased and the current response is relatively reduced; if bloodhas a low hematocrit value (low Hct value), the viscosity of the bloodis reduced and the current response is relatively increased.

Next, referring to FIGS. 2 and 22, the measurement flow in the firstbiological information measurement mode A, the pre-processingapplication mode B, the voltage application stop mode C, and the secondbiological information measurement mode D will be described in moredetail. FIG. 22 is an operational flowchart of a biological informationmeasurement device of this embodiment.

Before use, a plurality of biosensors 2 (shown in FIG. 2) are stored ina dry container (not shown). The biosensors 2 are taken out of the drycontainer one by one every time the glucose value (i.e., the bloodglucose level or the second biological information) is measured. Then,as shown in FIG. 1, one end of the biosensor 2 is inserted into theinsertion port 3 (S1: “Attach biosensor” in FIG. 22) and electricallyconnected to the input terminal portion 9. Consequently, the controlportion 19 recognizes that the biosensor 2 has been attached to theinput terminal portion 9, and starts a measuring operation (S2;“Activate power source of measurement device” in FIG. 22).

In this state, a drop of blood of a user has not been placed on theblood inlet 15 yet.

With the start of the measuring operation, the control portion 19 allowsan applied voltage to be supplied to each of the blood componentmeasurement working electrode 6, the blood component measurement counterelectrode 7, and the blood component introduction detecting electrode 8of the biosensor 2 via the voltage application portion 17 and the inputterminal portion 9 (S3: “Apply voltage to measurement working electrode,measurement counter electrode, and detecting electrode” in FIG. 22).

In this embodiment, the applied voltage supplied to each of the bloodcomponent measurement working electrode 6, the blood componentmeasurement counter electrode 7, and the blood component introductiondetecting electrode 8 is, e.g., 0.5 V.

Next, a user pricks their finger or the like with a lancet to draw bloodand places a drop of blood on the blood inlet 15 of the biosensor 2 (S4:“Place drop of blood on inlet of biosensor” in FIG. 22).

Then, a current begins to flow between the blood component measurementworking electrode 6 and the blood component measurement counterelectrode 7 and between the blood component measurement workingelectrode 6 and the blood component introduction detecting electrode 8.This current is converted to a voltage by the current-voltage converter18, and subsequently the voltage is converted to a digital value by theA/D converter 20. Thereafter, the determination portion 21 of thecontrol portion 19 makes a determination.

Specifically, the control portion 19 measures a value of the currentflowing between the blood component measurement working electrode 6 andthe blood component measurement counter electrode 7, and compares avoltage value that is proportional to the current value with apredetermined threshold value (e.g., 10 mV). If the voltage value is notless than the threshold value, then the control portion 19 measures avalue of the current flowing between the blood component measurementworking electrode 6 and the blood component introduction detectingelectrode 8.

If the voltage value that is proportional to the value of the currentflowing between the blood component measurement working electrode 6 andthe blood component measurement counter electrode 7 is less than thethreshold value, the determination portion 21 of the control portion 19determines that the drop of blood still has not sufficiently permeatedthe reagent 11, and repeats the above comparison until the value of thecurrent flowing between the blood component measurement workingelectrode 6 and the blood component measurement counter electrode 7 isnot less than the threshold value (S5: “Current flowing betweenmeasurement working electrode and measurement counter electrode≥Threshold value” in FIG. 22).

Similarly, the control portion 19 measures a value of the currentflowing between the blood component measurement working electrode 6 andthe blood component introduction detecting electrode 8, compares avoltage value that is proportional to the current value with apredetermined threshold value (e.g., 10 mV), and determines whether thevoltage value is not less than the threshold value. If the value is lessthan the threshold value, it is determined that the drop of blood stillhas not sufficiently permeated the reagent 11 and the blood componentintroduction detecting electrode 8, and the above comparison is repeateduntil the value is not less than the threshold value (S6: “Currentflowing between measurement working electrode and detecting electrode≥Threshold value” in FIG. 22).

Then, if the current value is not less than the threshold value in thestep S5 and the following step S6 in FIG. 22, the determination portion21 of the control portion 19 determines that the amount of the bloodthat has been introduced is large enough to be measured.

Next, when it is determined that the amount of the blood that has beenintroduced is large enough to be measured, the control portion 19applies, e.g., a voltage of 1.0 to 3.0 V (the applied voltage is 2.5 Vinthis embodiment) between the hematocrit measurement working electrode 5and the blood component measurement counter electrode 7 for anapplication time of 0.01 to 3.0 seconds (the application time is 0.5seconds in this embodiment) in the first biological informationmeasurement mode A (S7: “Apply voltage between hematocrit workingelectrode and measurement counter electrode to calculate hematocritvalue” in FIG. 22).

As can be seen from FIG. 2, there is a certain space (e.g., 0.01 mm to10 mm) between the hematocrit measurement working electrode 5 and theblood component measurement counter electrode 7, and no reagent such asan electron carrier is present in this space.

Therefore, only the blood flowing into the space between the hematocritmeasurement working electrode 5 and the blood component measurementcounter electrode 7 serves as an electron carrier. Consequently, anoxidation current that depends on the hematocrit value (the firstbiological information) can be detected without the influence of thereagent 11.

The oxidation current is recognized as a voltage value by the controlportion 19 via the current-voltage converter 18 and the A/D converter20.

One of the characteristics of this embodiment is that the voltage to beapplied in the pre-processing application mode B and the voltageapplication time during which a voltage is applied between the bloodcomponent measurement counter electrode 7 and the blood componentmeasurement working electrode 6 in the second biological informationmeasurement mode D can be changed based on the oxidation current (whichhas been converted to a voltage value) that depends on the hematocritvalue (the first biological information) and is recognized by thecontrol portion 19.

Specifically, in this embodiment, the voltage to be applied in thepre-processing application mode B can be determined according to theoxidation current (which has been converted to a voltage value) thatdepends on the detected hematocrit value (the first biologicalinformation), using a management table containing hematocrit values (thefirst biological information) and applied voltages, application times,etc. for measuring the glucose, which has been previously stored in thememory 24.

In other words, if blood has a high hematocrit value (high Hct value),the viscosity of the blood is increased and the current response isrelatively reduced during the measurement of the glucose. Therefore, thehigh-Hct blood requires a voltage to achieve a high current response. Ifblood has a low hematocrit value (low Hct value), the viscosity of theblood is reduced and the current response is relatively increased duringthe measurement of the glucose. Therefore, the low-Hct blood requires avoltage to achieve a low current response.

In this embodiment, e.g., the memory 24 stores settings of 0.75 V for ahematocrit value (the first biological information) of 20%, 0.35 V for ahematocrit value of 45%, and 0.15 V for a hematocrit value of 60%. Thecontrol portion 19 appropriately selects the voltage to be appliedaccording to these hematocrit values (S8: “Determine pre-processingvoltage to be applied and final application time according to hematocritvalue” in FIG. 22). In this embodiment, the voltage to be appliedaccording to the above hematocrit values may be modified by the ambienttemperature. The ambient temperature can be measured by a conventionallyknown method for measuring the ambient temperature, which will bedescribed later. Such a modification is made because the reactionbetween the glucose in the blood and the oxidoreductase is an enzymereaction that is affected by the ambient temperature. Similarly, thepredetermined time during which a voltage is applied may also bemodified by the ambient temperature.

In this embodiment, when the hematocrit value (the first biologicalinformation) represents a first hematocrit value in the memory 24, afirst voltage is applied to the second input terminal and the thirdinput terminal in the pre-processing application mode, and when thehematocrit value represents a second hematocrit value in the memory 24,a second voltage is applied to the second input terminal and the thirdinput terminal in the pre-processing application mode. The firsthematocrit value may be selected to be larger than the second hematocritvalue, and the first voltage may be selected to be smaller than thesecond voltage.

Alternatively, in this embodiment, when the hematocrit value (the firstbiological information) represents a first hematocrit value in thememory 24, a first voltage is applied to the second input terminal andthe third input terminal in the pre-processing application mode, whenthe hematocrit value represents a second hematocrit value in the memory24, a second voltage is applied to the second input terminal and thethird input terminal in the pre-processing application mode, and whenthe hematocrit value represents a third hematocrit value in the memory24, a third voltage is applied to the second input terminal and thethird input terminal in the pre-processing application mode. The firsthematocrit value may be selected to be larger than the second hematocritvalue and the third hematocrit value, and the second hematocrit valuemay be selected to be larger than the third hematocrit value. The firstvoltage may be selected to be smaller than the second voltage and thethird voltage, and the second voltage may be selected to be smaller thanthe third voltage.

Next, in this embodiment, the control portion 19 applies the voltagethat has been determined according to the measured hematocrit value (thefirst biological information) between the blood component measurementworking electrode 6 and the blood component measurement counterelectrode 7, e.g., for a predetermined time of 0.5 to 4.0 seconds (for2.0 seconds in this embodiment) in the pre-processing application mode B(S9: “Apply determined voltage between measurement working electrode andmeasurement counter electrode” in FIG. 22).

Thereafter, in this embodiment, the control portion 19 stops theapplication of the voltage to all the electrodes (the hematocritmeasurement working electrode 5, the blood component measurement workingelectrode 6, the blood component measurement counter electrode 7, andthe blood component introduction detecting electrode 8) of the biosensor2 for about 0.1 to 5.0 seconds (for 1.0 second in this embodiment) inorder to further accelerate the reaction between the glucose in theblood and the reagent 11 containing the oxidoreductase and the electroncarrier in the voltage application stop mode C (S10: “Stop voltageapplication” in FIG. 22).

Then, in the voltage application stop mode C, the glucose in the bloodreacts with the oxidoreductase for a certain period of time.

In the next second biological information measurement mode D, thecontrol portion 19 applies a voltage between the blood componentmeasurement working electrode 6 and the blood component measurementcounter electrode 7, oxidizes the reduced electron carrier that isgenerated on the blood component measurement working electrode 6 by theenzyme reaction, and detects the oxidation current, thereby measuring aglucose (blood glucose) value (the second biological information).

The reaction time between the glucose and the oxidoreductase in thesecond biological information measurement mode D is, e.g., 0.5 to 20seconds, and more preferably 0.5 to 10 seconds. In this embodiment, thevoltage application time during which a voltage is applied between theblood component measurement counter electrode 7 and the blood componentmeasurement working electrode 6 in the second biological informationmeasurement mode D can be changed based on the first biologicalinformation (the hematocrit value) in the first biological informationmeasurement mode A.

Specifically, in this embodiment, a voltage of 0.05 to 1.0 V, and morepreferably a voltage of 0.1 to 0.8 V (0.25 V in this embodiment) isapplied between the blood component measurement working electrode 6 andthe blood component measurement counter electrode 7 while the voltageapplication time can be changed based on the first biologicalinformation (the hematocrit value) in the first biological informationmeasurement mode A (S11: “Apply voltage finally between measurementworking electrode and measurement counter electrode” in FIG. 22).

Specifically, when the first biological information, i.e., thehematocrit value is 20% in the first biological information measurementmode A, the voltage application time is 2.0 seconds, during which avoltage is applied between the blood component measurement counterelectrode 7 and the blood component measurement working electrode 6 inthe second biological information measurement mode D.

When the hematocrit value is 45%, the voltage application time is 1.0second, during which a voltage is applied between the blood componentmeasurement counter electrode 7 and the blood component measurementworking electrode 6 in the second biological information measurementmode D.

When the hematocrit value is 60%, the voltage application time is 0.8seconds, during which a voltage is applied between the blood componentmeasurement counter electrode 7 and the blood component measurementworking electrode 6 in the second biological information measurementmode D.

In this embodiment, when the hematocrit value (the first biologicalinformation) represents a first hematocrit value in the memory 24, afourth voltage is applied to the second input terminal and the thirdinput terminal for a first period of time in the second biologicalinformation measurement mode, and when the hematocrit value represents asecond hematocrit value in the memory 24, a fourth voltage is applied tothe second input terminal and the third input terminal for a secondperiod of time in the second biological information measurement mode.The first hematocrit value may be selected to be larger than the secondhematocrit value, and the second period of time may be selected to belonger than the first period of time.

Alternatively, in this embodiment, when the hematocrit value (the firstbiological information) represents a first hematocrit value in thememory 24, a fourth voltage is applied to the second input terminal andthe third input terminal for a first period of time in the secondbiological information measurement mode, when the hematocrit valuerepresents a second hematocrit value in the memory 24, a fourth voltageis applied to the second input terminal and the third input terminal fora second period of time in the second biological information measurementmode, and when the hematocrit value represents a third hematocrit valuein the memory 24, a fourth voltage is applied to the second inputterminal and the third input terminal for a third period of time in thesecond biological information measurement mode. The first hematocritvalue may be selected to be larger than the second hematocrit value andthe third hematocrit value, and the second hematocrit value may beselected to be larger than the third hematocrit value. The second periodof time and the third period of time may be selected to be longer thanthe first period of time, and the third period of time may be selectedto be longer than the second period of time.

Thereafter, in this embodiment, the control portion 19 calculates theglucose value (the second biological information).

The calculated glucose value (the second biological information) issubjected to a conventionally known temperature correction (S12:“Measure and Correct glucose value in determined final application time”in FIG. 22).

The temperature correction is performed because the enzyme reaction formeasuring the glucose value is affected by the ambient temperature.However, in the step S8 of determining a pre-processing voltage to beapplied according to the hematocrit value, as shown in FIG. 3, if thevoltage to be applied and/or the application time according to thehematocrit value are modified by the ambient temperature, the glucosevalue may be either corrected or not corrected at this stage. On theother hand, in the step S8 of determining a pre-processing voltage to beapplied according to the hematocrit value, as shown in FIG. 3, if thevoltage to be applied and the application time according to thehematocrit value are not modified by the ambient temperature, theglucose value needs to be corrected at this stage.

The glucose value thus corrected is displayed on the display portion 22as a final glucose (blood glucose) value (the second biologicalinformation) (S13: “Display glucose value” in FIG. 22).

One of the characteristics of this embodiment is that the voltage to beapplied in the pre-processing application mode B can be changed based onthe oxidation current (which has been converted to a voltage value) thatdepends on the hematocrit value (the first biological information) andis recognized by the control portion 19, and that the voltageapplication time in the second biological information measurement mode Dcan be changed based on the first biological information (the hematocritvalue) in the first biological information measurement mode A.Consequently, the blood glucose level displayed on the display portion22 can achieve extremely high accuracy.

Hereinafter, this point will be described with reference to FIGS. 11 to21.

FIG. 18 is a graph showing a change in an output voltage (mV) with ablood glucose level in a biological information measurement device ofanother embodiment of the present invention. Specifically, in thisembodiment, FIG. 18 illustrates how the output of the A/D converter 20(FIG. 1) is changed with the blood glucose level in the secondbiological information measurement mode D when the hematocrit values are20%, 45%, and 60% (corresponding to the state before the correction inthe step S12 in FIG. 22). As can be seen from FIG. 18, the outputvoltage increases with increasing the blood glucose level no matterwhether the hematocrit value is 20%, 45%, or 60%.

On the other hand, FIG. 11 is a graph showing a change in an outputvoltage (mV) with a blood glucose level in a biological informationmeasurement device of a conventional example. Specifically, in theconventional example, FIG. 11 illustrates how the output of the A/Dconverter 20 (FIG. 1) is changed with the blood glucose level in thesecond biological information measurement mode D when the hematocritvalues are 20%, 45%, and 60%. As can be seen from FIG. 11, similarly toFIG. 18, the output voltage increases with increasing the blood glucoselevel no matter whether the hematocrit value is 20%, 45%, or 60%.

Comparing FIG. 18 (this embodiment) and FIG. 11 (the conventionalexample) shows that a variation in the detected blood glucose level (thesecond biological information) is small even if the hematocrit values(the first biological information) differ in this embodiment. Forexample, in FIG. 11 (the conventional example), when the blood glucoselevel is 350 mg/dl, the output voltage is 280 mV for a hematocrit valueof 45%, but the output voltage is increased to 390 mV for a hematocritvalue of 20%, resulting in a difference of 110 mV.

Moreover, in FIG. 11 (the conventional example), while the outputvoltage is 280 mV for a hematocrit value of 45%, the output voltage isreduced to 200 mV for a hematocrit value of 60%, resulting in adifference of 80 mV.

On the other hand, in FIG. 18 (this embodiment), when the blood glucoselevel is 350 mg/dl, the output voltage is 330 mV for a hematocrit valueof 45%, and the output voltage is 330 mV for a hematocrit value of 20%,making no difference.

Moreover, in FIG. 18 (this embodiment), while the output voltage is 330mV for a hematocrit value of 45%, the output voltage is 300 mV for ahematocrit value of 60%, making only a difference of 30 mV.

As a result of not only changing the voltage to be applied between theblood component measurement working electrode 6 and the blood componentmeasurement counter electrode 7 in the pre-processing application modeB, as shown in FIG. 15, but also changing the voltage application timein the second biological information measurement mode D, this embodimentcan reduce a difference in the output voltage between the hematocritvalues.

In other words, this embodiment deals with the following points. Asdescribed above, if blood has a high hematocrit value (high Hct value),the viscosity of the blood is increased and the current response isrelatively reduced during the measurement of the glucose. Therefore, thehigh-Hct blood requires a voltage to achieve a high current response. Ifblood has a low hematocrit value (low Hct value), the viscosity of theblood is reduced and the current response is relatively increased duringthe measurement of the glucose. Therefore, the low-Hct blood requires avoltage to achieve a low current response.

In contrast, the conventional example applies the same voltage betweenthe blood component measurement working electrode 6 and the bloodcomponent measurement counter electrode 7 in the pre-processingapplication mode B regardless of the hematocrit value (FIG. 11), so thatthe output voltage varies greatly. FIG. 11 is a graph showing a changein an output voltage (mV) with a blood glucose level in a biologicalinformation measurement device of the conventional example.

FIG. 12 is a graph showing a difference in sensitivity of an outputvoltage (mV) with respect to a hematocrit value in a biologicalinformation measurement device of the conventional example.Specifically, FIG. 12 illustrates a difference (the degree of influence)in each of the samples with blood glucose levels of 100 mg/dl and 350mg/dl when their hematocrit values are 20% and 60% as compared to 45% inthe conventional example.

FIG. 12 (the conventional example) shows that both the samples withblood glucose levels of 100 mg/dl and 350 mg/dl have a difference of 35%or more on the hematocrit 20% side and a difference of 20% or more onthe hematocrit 60% side from the hematocrit value 45%.

Thus, in the conventional example, the output voltage of the A/Dconverter 20 varies greatly depending on the hematocrit value, as can beseen from FIGS. 11 and 12.

The conventional example also has made an attempt to calculate the finalblood glucose level by correcting the output voltage of the A/Dconverter 20 in accordance with the subsequently detected hematocritvalue.

However, in this conventional example, as shown in FIG. 13, the samplewith a blood glucose level of 100 mg/dl has a variation of +7.5% to−4.0% when the hematocrit value is 20%, a variation of +9.0% to −5.0%when the hematocrit value is 45%, and a variation of +9.5% to −7.0% whenthe hematocrit value is 60%. FIG. 13 is a graph showing a difference insensitivity of an output voltage (mV) with respect to a hematocrit valuein a biological information measurement device of the conventionalexample.

As shown in FIG. 14, the sample with a blood glucose level of 350 mg/dlhas a variation of +8.0% to −4.0% when the hematocrit value is 20%, avariation of +10.0% to −6.0% when the hematocrit value is 45%, and avariation of +11.0% to −7.5% when the hematocrit value is 60%. FIG. 14is a graph showing a difference in sensitivity of an output voltage (mV)with respect to a hematocrit value in a biological informationmeasurement device of the conventional example.

Even if subsequent corrections are performed while there is such a greatvariation, the final blood glucose level will still vary significantly.

Thus, the measurement accuracy is low in the conventional biologicalinformation measurement device.

Contrary to the conventional example, FIG. 19 is a graph showing adifference in sensitivity of an output voltage (mV) with respect to ahematocrit value in a biological information measurement device of thisembodiment. Specifically, FIG. 19 illustrates a difference (the degreeof influence) in each of the samples with blood glucose levels of 100mg/dl and 350 mg/dl when their hematocrit values are 20% and 60% ascompared to 45% in this embodiment.

FIG. 19 (this embodiment) shows that both the samples with blood glucoselevels of 100 mg/dl and 350 mg/dl have only a difference of about 2% onthe hematocrit 20% side and only a difference of about 9% on thehematocrit 60% side from the hematocrit value 45%.

Thus, in this embodiment, the output voltage of the A/D converter 20varies slightly depending on the hematocrit value, as can be seen fromFIGS. 18 and 19.

Therefore, this embodiment shows only a small variation when the finalblood glucose level is calculated from the output voltage of the A/Dconverter 20.

This point will be further described with reference to FIGS. 20 and 21.FIGS. 20 and 21 are graphs showing a difference in sensitivity of anoutput voltage (mV) with respect to a hematocrit value in a biologicalinformation measurement device of this embodiment. As shown in FIG. 20,the sample with a blood glucose level of 100 mg/dl has substantially novariation when the hematocrit value is 20%, only a variation of +2.5% to0.0% when the hematocrit value is 45%, and only a variation of +2.5% to−2.5% when the hematocrit value is 60%.

As shown in FIG. 21, the sample with a blood glucose level of 350 mg/dlhas substantially no variation when the hematocrit value is 20%, only avariation of +3.0% to 0.0% when the hematocrit value is 45%, and only avariation of +0.0% to −3.0% when the hematocrit value is 60%.

Therefore, in this embodiment, since the blood glucose level itself ismeasured under the conditions that are not much affected by thehematocrit value, the measurement accuracy can be improved.

This embodiment performs a temperature correction in the step S12 inFIG. 22 in order to reduce the influence of the temperature, so that themeasurement accuracy can be improved further.

In this embodiment, if the resultant hematocrit value (the firstbiological information) is a standard value (e.g., the hematocrit valueis 42), it is not necessary to change the voltage to be applied in thepre-processing application mode B and the voltage application time inthe second biological information measurement mode D.

Embodiment 3

Embodiment 1 can change a voltage to be applied in the pre-processingapplication mode B, and Embodiment 2 can change a voltage to be appliedin the pre-processing application mode B and an application time in thesecond biological information measurement mode D. Using theconfigurations shown in FIGS. 1 and 2, the control portion 19 mayperform a control operation as shown in FIG. 23.

FIG. 23 is a diagram showing the state of a voltage applied over time ina biological information measurement device of yet another embodiment ofthe present invention. The control operation shown in FIG. 23 mainlyperforms the first biological information measurement mode A and thesecond biological information measurement mode D.

Specifically, in this embodiment, a hematocrit value (the firstbiological information) is measured in the first biological informationmeasurement mode A, and then the second biological informationmeasurement mode D is performed immediately after a short interval(which is shorter than the stop time of the voltage application stopmode C in Embodiments 1 and 2). In performing the second biologicalinformation measurement mode D, based on the hematocrit value (the firstbiological information) measured in the first biological informationmeasurement mode A, the control portion 19 can change a voltage value tobe applied to the blood component measurement counter electrode 7 andthe blood component measurement working electrode 6 in the secondbiological information measurement mode D, or further can change avoltage application time during which a voltage is applied to the bloodcomponent measurement counter electrode 7 and the blood componentmeasurement working electrode 6 in the second biological informationmeasurement mode D.

FIG. 24 is a diagram showing the state of a voltage applied over time ina biological information measurement device of yet another embodiment ofthe present invention. The control operation shown in FIG. 24, which isyet another embodiment of the present invention, performs the firstbiological information measurement mode A, the voltage application stopmode C, and the second biological information measurement mode D.

Specifically, in this embodiment, a hematocrit value (the firstbiological information) is measured in the first biological informationmeasurement mode A, and then the voltage application stop mode C isperformed to stop the application of the voltage to the blood componentmeasurement counter electrode 7 and the blood component measurementworking electrode 6, and subsequently the second biological informationmeasurement mode D is performed. In performing the second biologicalinformation measurement mode D, based on the hematocrit value (the firstbiological information) measured in the first biological informationmeasurement mode A, the control portion 19 can change a voltage value tobe applied to the blood component measurement counter electrode 7 andthe blood component measurement working electrode 6 in the secondbiological information measurement mode D, or further can change avoltage application time during which a voltage is applied to the bloodcomponent measurement counter electrode 7 and the blood componentmeasurement working electrode 6 in the second biological informationmeasurement mode D, or still further can change a stop time during whichthe application of the voltage to all the electrodes (the hematocritmeasurement working electrode 5, the blood component measurement workingelectrode 6, the blood component measurement counter electrode 7, andthe blood component introduction detecting electrode 8) is stopped inthe voltage application stop mode C.

FIG. 25 is a diagram showing the state of a voltage applied over time ina biological information measurement device of yet another embodiment ofthe present invention. The control operation shown in FIG. 25, which isyet another embodiment of the present invention, performs the firstbiological information measurement mode A and the second biologicalinformation measurement mode D.

Specifically, in this embodiment, before starting the measurement (i.e.,at the time of waiting for the detection of blood), a hematocrit value(the first biological information) is measured in the first biologicalinformation measurement mode A, and the second biological informationmeasurement mode D is performed immediately. In performing the secondbiological information measurement mode D, based on the hematocrit value(the first biological information) measured in the first biologicalinformation measurement mode A, the control portion 19 can change avoltage value to be applied to the blood component measurement counterelectrode 7 and the blood component measurement working electrode 6 inthe second biological information measurement mode D, or further canchange a voltage application time during which a voltage is applied tothe blood component measurement counter electrode 7 and the bloodcomponent measurement working electrode 6 in the second biologicalinformation measurement mode D.

FIG. 26 is a diagram showing the state of a voltage applied over time ina biological information measurement device of yet another embodiment ofthe present invention. The control operation shown in FIG. 26, which isyet another embodiment of the present invention, performs the firstbiological information measurement mode A, the voltage application stopmode C, and the second biological information measurement mode D.

Specifically, in this embodiment, before starting the measurement (i.e.,at the time of waiting for the detection of blood), a hematocrit value(the first biological information) is measured in the first biologicalinformation measurement mode A, and then (when the measurement isstarted) the voltage application stop mode C is performed to stop theapplication of the voltage to the blood component measurement counterelectrode 7 and the blood component measurement working electrode 6, andsubsequently the second biological information measurement mode D isperformed. In performing the second biological information measurementmode D, based on the hematocrit value (the first biological information)measured in the first biological information measurement mode A, thecontrol portion 19 can change a voltage value to be applied to the bloodcomponent measurement counter electrode 7 and the blood componentmeasurement working electrode 6 in the second biological informationmeasurement mode D, or further can change a voltage application timeduring which a voltage is applied to the blood component measurementcounter electrode 7 and the blood component measurement workingelectrode 6 in the second biological information measurement mode D, orstill further can change a stop time during which the application of thevoltage to all the electrodes (the hematocrit measurement workingelectrode 5, the blood component measurement working electrode 6, theblood component measurement counter electrode 7, and the blood componentintroduction detecting electrode 8) is stopped in the voltageapplication stop mode C.

FIG. 27 is a diagram showing the state of a voltage applied over time ina biological information measurement device of yet another embodiment ofthe present invention. The control operation shown in FIG. 27, which isyet another embodiment of the present invention, performs thepre-processing application mode B, the first biological informationmeasurement mode A, the voltage application stop mode C, and the secondbiological information measurement mode D.

Specifically, in this embodiment, an approximate glucose value iscalculated in the pre-processing application mode B, and then based onthe hematocrit value (the first biological information) in the firstbiological information measurement mode A, the control portion 19 canchange a voltage value to be applied to the blood component measurementcounter electrode 7 and the blood component measurement workingelectrode 6 in the second biological information measurement mode D anda voltage application time during which a voltage is applied to theblood component measurement counter electrode 7 and the blood componentmeasurement working electrode 6 in the second biological informationmeasurement mode D. Moreover, the voltage application stop mode C or ashort interval (which is shorter than the stop time of the voltageapplication stop mode C in Embodiments 1 and 2) may be provided beforeand after the first biological information measurement mode A.

In this embodiment, if the resultant hematocrit value (the firstbiological information) is a standard value (e.g., the hematocrit valueis 42), it is not necessary to change the voltage to be applied and thevoltage application time in the second biological informationmeasurement mode D.

INDUSTRIAL APPLICABILITY

As described above, the present invention is directed to a biologicalinformation measurement device to which a biosensor is to be attached.The biosensor includes a first electrode, a second electrode, a thirdelectrode, and a reagent portion provided between the second electrodeand the third electrode. The biological information measurement deviceincludes the following: a first input terminal to be connected to thefirst electrode; a second input terminal to be connected to the secondelectrode; a third input terminal to be connected to the thirdelectrode; a voltage application portion that applies a voltage to thefirst input terminal, the second input terminal, and the third inputterminal; a determination portion that is connected to the first inputterminal, the second input terminal, and the third input terminal; acontrol portion that is connected to the determination portion and thevoltage application portion; and a display portion that is connected tothe control portion. The control portion is configured to perform afirst biological information measurement mode in which first biologicalinformation is measured based on a current flowing through the firstinput terminal and a second biological information measurement mode inwhich second biological information is measured by applying a voltage tothe second input terminal and the third input terminal after the firstbiological information measurement mode. The display portion isconfigured to display the second biological information. The controlportion is configured to be able to change at least one of i) a voltagevalue to be applied to the second input terminal and the third inputterminal in the second biological information measurement mode and ii) avoltage application time during which a voltage is applied to the secondinput terminal and the third input terminal in the second biologicalinformation measurement mode based on the first biological informationin the first biological information measurement mode. Thus, the presentinvention can improve the measurement accuracy.

According to the present invention, at least one of the voltage value tobe applied to the second input terminal and the third input terminal inthe second biological information measurement mode and the voltageapplication time during which a voltage is applied to the second inputterminal and the third input terminal in the second biologicalinformation measurement mode can be changed based on the firstbiological information in the first biological information measurementmode. For example, a hematocrit value is measured in the firstbiological information measurement mode, and the biological information,e.g., a blood glucose level is measured based on this hematocrit valuein the second biological information measurement mode.

As described above, the present invention is directed to a biologicalinformation measurement device to which a biosensor is to be attached.The biosensor includes a first electrode, a second electrode, a thirdelectrode, and a reagent portion provided between the second electrodeand the third electrode. The biological information measurement deviceincludes the following: a first input terminal to be connected to thefirst electrode; a second input terminal to be connected to the secondelectrode; a third input terminal to be connected to the thirdelectrode; a voltage application portion that applies a voltage to thefirst input terminal, the second input terminal, and the third inputterminal; a determination portion that is connected to the first inputterminal, the second input terminal, and the third input terminal; acontrol portion that is connected to the determination portion and thevoltage application portion; and a display portion that is connected tothe control portion. The control portion is configured to perform afirst biological information measurement mode in which first biologicalinformation is measured based on a current flowing through the firstinput terminal, a pre-processing application mode in which a voltage isapplied to the second input terminal and the third input terminal afterthe first biological information measurement mode, a voltage applicationstop mode in which the application of the voltage to the second inputterminal and the third input terminal is stopped after thepre-processing application mode, and a second biological informationmeasurement mode in which second biological information is measured byapplying a voltage to the second input terminal and the third inputterminal after the voltage application stop mode. The display portion isconfigured to display the second biological information. The controlportion is configured to be able to change a voltage value to be appliedto the second input terminal and the third input terminal in thepre-processing application mode based on the first biologicalinformation in the first biological information measurement mode. Thus,the present invention can improve the measurement accuracy.

According to the present invention, the voltage value to be applied tothe second input terminal and the third input terminal in thepre-processing application mode can be changed based on the firstbiological information in the first biological information measurementmode. For example, a hematocrit value is measured in the firstbiological information measurement mode, and the biological information,e.g., a blood glucose level is measured based on this hematocrit valuein the second biological information measurement mode.

As described above, the present invention is directed to a biologicalinformation measurement device to which a biosensor is to be attached.The biosensor includes a first electrode, a second electrode, a thirdelectrode, and a reagent portion provided between the second electrodeand the third electrode. The biological information measurement deviceincludes the following: a first input terminal to be connected to thefirst electrode; a second input terminal to be connected to the secondelectrode; a third input terminal to be connected to the thirdelectrode; a voltage application portion that applies a voltage to thefirst input terminal, the second input terminal, and the third inputterminal; a determination portion that is connected to the first inputterminal, the second input terminal, and the third input terminal; acontrol portion that is connected to the determination portion and thevoltage application portion; and a display portion that is connected tothe control portion. The control portion is configured to perform afirst biological information measurement mode in which first biologicalinformation is measured based on a current flowing through the firstinput terminal, a pre-processing application mode in which a voltage isapplied to the second input terminal and the third input terminal afterthe first biological information measurement mode, a voltage applicationstop mode in which the application of the voltage to the second inputterminal and the third input terminal is stopped after thepre-processing application mode, and a second biological informationmeasurement mode in which second biological information is measured byapplying a voltage to the second input terminal and the third inputterminal after the voltage application stop mode. The display portion isconfigured to display the second biological information. The controlportion is configured to be able to change a voltage value to be appliedto the second input terminal and the third input terminal in thepre-processing application mode based on the first biologicalinformation in the first biological information measurement mode. Thecontrol portion is configured to be able to change a voltage applicationtime during which a voltage is applied to the second input terminal andthe third input terminal in the second biological informationmeasurement mode based on the first biological information in the firstbiological information measurement mode. Thus, the present invention canimprove the measurement accuracy.

According to the present invention, the voltage value to be applied tothe second input terminal and the third input terminal in thepre-processing application mode can be changed based on the firstbiological information in the first biological information measurementmode, and the voltage application time during which a voltage is appliedto the second input terminal and the third input terminal in the secondbiological information measurement mode can be changed based on thefirst biological information in the first biological informationmeasurement mode. For example, a hematocrit value is measured in thefirst biological information measurement mode, and the biologicalinformation, e.g., a blood glucose level is measured based on thishematocrit value in the second biological information measurement mode.

Therefore, according to the present invention, since the blood glucoselevel itself is measured under the conditions that are not much affectedby the hematocrit value, the measurement accuracy can be improved.

It is expected that the present invention will be used as a biologicalinformation detector for detecting the biological information such as ablood glucose level.

DESCRIPTION OF REFERENCE NUMERALS

-   -   1 Main body case    -   2 Biosensor    -   3 Insertion port    -   4 Insulating substrate    -   5 Hematocrit measurement working electrode    -   6 Blood component measurement working electrode    -   7 Blood component measurement counter electrode    -   8 Blood component introduction detecting electrode    -   9 Input terminal portion    -   10 Reagent portion    -   11 Reagent    -   12 Spacer    -   13 Cover    -   14 Blood supply path    -   15 Blood inlet    -   16 Air hole    -   17 Voltage application portion    -   18 Current-voltage converter    -   19 Control portion    -   20 A/D converter    -   21 Determination portion    -   22 Display portion    -   23 Power source    -   24 Memory    -   25 Clock    -   26 Correction portion

The invention claimed is:
 1. A biological information measurement deviceto which a biosensor is to be attached, the biosensor comprising a firstelectrode, a second electrode, a third electrode, and a reagent portionprovided between the second electrode and the third electrode, thebiological information measurement device comprising: a first inputterminal to be connected to the first electrode; a second input terminalto be connected to the second electrode; a third input terminal to beconnected to the third electrode; a voltage application portion thatapplies a voltage to the first input terminal, the second inputterminal, and the third input terminal; and a control portion that isconnected to the voltage application portion, wherein the controlportion is configured to perform a first biological informationmeasurement mode immediately after determining that the amount of theblood that has introduced is large enough to be measured, and then asecond biological information measurement mode, in the first biologicalinformation measurement mode, first biological information is measuredbased on a current flowing through the first input terminal, and in thesecond biological information measurement mode, second biologicalinformation is measured by applying a voltage to the second inputterminal and the third input terminal, the first biological informationis a hematocrit value, when the hematocrit value represents a firsthematocrit value, the control portion applies a first voltage to thesecond input terminal and the third input terminal in the secondbiological information measurement mode, or applies a voltage to thesecond input terminal and the third input terminal for a firstapplication time in the second biological information measurement mode,when the hematocrit value represents a second hematocrit value, thecontrol portion applies a second voltage to the second input terminaland the third input terminal in the second biological informationmeasurement mode, or applies a voltage to the second input terminal andthe third input terminal for a second application time in the secondbiological information measurement mode, the first hematocrit value islarger than the second hematocrit value, the first voltage is smallerthan the second voltage, and the second application time is longer thanthe first application time.
 2. The biological information measurementdevice according to claim 1, wherein the voltage applied in the firstbiological information measurement mode is 1.0 to 3.0 V.
 3. Thebiological information measurement device according to claim 1, whereinthe application time of the voltage applied in the first biologicalinformation measurement mode is 0.01 to 3.0 seconds.
 4. The biologicalinformation measurement device according to claim 2, wherein theapplication time of the voltage applied in the first biologicalinformation measurement mode is 0.01 to 3.0 seconds.